Small Bowel Mucosal Disease: Small Bowel Mucosal Disease: Beyond Celiac Disease

0:00Welcome to Board Pearls. This is episode one of one of the Small Bowel Mucosal Disease chapter, in the Stomach and Small Bowel Disorders module. This episode covers the small bowel problems that sit beside celiac disease. A woman who feels better off wheat shows how celiac disease is excluded first, and how gluten sensitivity, wheat allergy, and fermentable carbohydrate intolerance are told apart. A man with villous atrophy and negative celiac serology shows why the medication list comes before more biopsies. A woman with other autoimmune diseases and diarrhea severe enough to need parenteral nutrition shows autoimmune enteropathy. A man back from India shows tropical sprue and why both folate and B12 fall. A farmer with years of migratory arthritis shows Whipple disease, the infection whose arthritis comes first. And a man with an old gastrectomy shows small intestinal bacterial overgrowth. For each, the case shows what must be excluded, which finding or test decides, and how the mechanism chooses the treatment.

1:02Here's the first patient. A thirty-three-year-old woman has bloating, crampy pain, loose stools, and fatigue that she links to bread and pasta, usually starting several hours after eating. Six months ago she cut out gluten on her own and feels much better. She wants to know whether she has celiac disease. She's never had hives, swelling, or wheezing after eating. She has no blood in her stool, no nighttime symptoms, and no weight loss.

1:26Her wheat-triggered symptoms could be celiac disease, non-celiac gluten sensitivity, wheat allergy, or fermentable carbohydrate intolerance. One thing must be excluded before any of the other labels, and that's celiac disease. It's tested on a gluten-containing diet, with tissue transglutaminase immunoglobulin A, IgA, and a total IgA level, and duodenal biopsies if the antibody is positive or suspicion remains. Inflammatory bowel disease should also be off the table. Gluten sensitivity, wheat allergy, and carbohydrate intolerance are diagnoses made only after those are excluded.

2:03She's already gluten-free, which lowers the antibody and heals the bowel, so a normal test now could be falsely negative. She has two options. She can go back on gluten, about ten grams a day, roughly three slices of wheat bread, for one to three months, and then be tested. Or she can have human leukocyte antigen, HLA, DQ2 and DQ8 testing.

2:23The genetic test works in only one direction. Celiac disease essentially requires one of those genes, so a negative result excludes it without a challenge. A positive result rules nothing in, because thirty to forty percent of people carry one of them, and she'd still need the gluten challenge. She chooses HLA testing and is negative for both. She doesn't have celiac disease, and her history has no blood, nighttime symptoms, or weight loss to suggest inflammatory bowel disease.

2:52That leaves three possibilities, separated first by timing, because their mechanisms work on different clocks.

2:59Wheat allergy is the fastest and most dangerous. It's immunoglobulin E, IgE, mediated, so symptoms come within minutes to a couple of hours: hives, swelling, wheezing, cramping with vomiting, and at worst anaphylaxis. One variant, wheat-dependent exercise-induced anaphylaxis, causes symptoms only when wheat is followed by exertion.

3:24Wheat allergy is diagnosed and managed differently from the other two. The diagnosis is made by an allergist, with skin prick testing or wheat-specific IgE, and an oral food challenge if it's unclear. It's the only one of the three that requires complete wheat avoidance, for safety rather than symptom control. Her symptoms start hours after eating, with no hives, swelling, or wheezing, so wheat allergy doesn't fit.

3:50Non-celiac gluten sensitivity is slower. Symptoms appear hours to days after gluten, with negative celiac serology, normal duodenal histology, and no wheat allergy. Patients often describe fatigue, weight loss, headache, brain fog, and sometimes eczema, ataxia, or numbness. It's more common in women, often in their thirties. Its mechanism isn't well defined and is probably mixed.

4:17Her negative HLA test doesn't exclude gluten sensitivity. About forty to fifty percent of patients with it carry DQ2 or DQ8, but its absence doesn't rule it out the way it rules out celiac disease. Biopsies may show slightly raised lymphocytes, but the villi are normal.

4:35Its formal diagnosis is a blinded gluten challenge. After at least four weeks on a strict gluten-free diet, the patient takes eight grams of gluten a day or a placebo for a week, then has a washout week, then crosses over for a week. A rise of about thirty percent or more in the symptom score on gluten counts as positive.

4:55The third possibility explains much of what used to be called gluten sensitivity. It's intolerance of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, FODMAPs. FODMAPs are short-chain carbohydrates the small bowel absorbs poorly. They draw water into the lumen, then reach the colon, where bacteria ferment them into gas, causing distension and pain.

5:21They come from familiar foods. Fructans are in wheat, onions, garlic, and artichokes. Galacto-oligosaccharides are in beans and lentils. Lactose is in dairy. Excess fructose is in apples, pears, and honey. Polyols, such as sorbitol and mannitol, are in sugar-free chewing gum.

5:39Her bloating, crampy pain, and loose stools after meals are also the irritable bowel picture, and in some patients gluten sensitivity is indistinguishable from irritable bowel. Fatigue, brain fog, and headache set some gluten-sensitive patients apart, but not reliably, and serum zonulin, proposed as a marker, isn't part of standard practice. What works is a structured dietary experiment: remove foods in a controlled way, then bring them back one group at a time. Both the blinded gluten challenge and the low-FODMAP diet are versions of that.

6:12Which experiment to run first depends on what in wheat is really making her sick. When people who believe they're gluten sensitive are given purified gluten or wheat fructans in a blinded crossover trial, the fructans reproduce their symptoms more reliably than the gluten does. Wheat is a major fructan source, so a gluten-free diet is also a lower-fructan diet. That's why she feels better, and it doesn't prove gluten is the culprit.

6:38The consequences of each label also favor starting with FODMAPs. A gluten-free label carries lifelong implications, while a FODMAP approach ends by restricting only the groups that trigger symptoms. So in a patient with irritable bowel-type symptoms like hers, the low-FODMAP approach comes before lifelong gluten avoidance.

6:57Her diet runs in three phases, supervised by a dietitian. Elimination restricts all FODMAP groups for four to six weeks. Reintroduction brings back each group separately to find her triggers. Personalization restricts only the groups that caused symptoms. Staying on blanket restriction is nutritionally harmful, changes the microbiome, and is harder than it needs to be. Validated in several randomized trials, the diet meaningfully improves pain and bloating in about half to two-thirds of patients with irritable bowel symptoms, and it's the preferred dietary therapy in irritable bowel syndrome whatever the celiac status.

7:35Reintroduction shows that fructans and excess fructose trigger her symptoms, but she tolerates small amounts of wheat. She limits the specific high-fructan and high-fructose foods that bother her and eats wheat in moderation. Symptoms that returned with purified gluten but not fructans would have pointed to gluten sensitivity and a gluten-reduced diet. Hives within an hour of wheat would have meant an allergist and strict avoidance. Three mechanisms lead to three different diets.

8:04The second patient has the biopsy of celiac disease but not the disease. A seventy-two-year-old man has had severe watery diarrhea for five months, up to ten times a day, with thirty pounds of weight loss. He's been admitted twice for dehydration and low potassium. His albumin is two point four, and he's mildly anemic. Duodenal biopsies show villous atrophy with increased lymphocytes. His tissue transglutaminase IgA is negative, with a normal total IgA. A gluten-free diet changed nothing. He takes olmesartan for hypertension, started four years ago, plus a statin and aspirin.

8:41He has seronegative villous atrophy that didn't respond to a gluten-free diet, so it probably isn't celiac disease, and the question is what it is. When villous atrophy looks like celiac disease but the serology is negative and the diet doesn't help, the medication list is read before more biopsies are ordered.

8:59The full list of causes is long, and drugs head it. It includes drugs, especially olmesartan, nonsteroidal anti-inflammatory drugs, NSAIDs, and mycophenolate; autoimmune enteropathy; common variable immunodeficiency, agammaglobulinemia, and other antibody deficiencies; small bowel Crohn disease; tropical sprue; Whipple disease; Giardia and intestinal tuberculosis; eosinophilic gastroenteritis; and intestinal lymphoma. Seronegative celiac disease, about five percent of celiac cases, is diagnosed only after these are excluded, with DQ2 or DQ8 present and a clear response to the diet, which he hasn't had.

9:41His medication list holds the likely answer. Olmesartan, an angiotensin receptor blocker, can cause a sprue-like enteropathy that closely imitates celiac disease, with severe diarrhea, weight loss, malabsorption, and villous atrophy. Other angiotensin receptor blockers, irbesartan, valsartan, and losartan, rarely do the same. The typical patient is around seventy and has taken the drug for about three years, often with a normocytic anemia, low albumin, and electrolyte disturbances from the diarrhea.

10:15The usual tests can't separate it from celiac disease or autoimmune enteropathy. Most patients with olmesartan enteropathy carry HLA-DQ2, so genetics doesn't help. The biopsy may show partial or total atrophy, sometimes a thick collagen band under the surface like collagenous sprue. About a third have anti-enterocyte antibodies, which overlaps with autoimmune enteropathy. Histology and serology can both mislead, and the history points the way.

10:46Proving it means stopping the drug. Stopping it is both the treatment and the diagnosis, with symptoms and histology improving over weeks to months, and olmesartan isn't restarted to prove the point. His olmesartan is switched to amlodipine. His diarrhea stops within three weeks, his potassium and albumin recover, and repeat biopsies months later show healed villi.

11:06His case shows the rule, and other drugs injure the small bowel in their own patterns. Chronic NSAIDs cause erosions, ulcers, and pathognomonic diaphragm-like strictures, thin concentric webs that narrow the lumen. They come from loss of protective prostaglandins and of the epithelial repair that depends on cyclooxygenase one. Capsule endoscopy shows them. They cause iron deficiency, protein loss, and partial obstruction, and they're treated by stopping the NSAID, replacing iron, and dilating or resecting symptomatic strictures.

11:40Mycophenolate injures a different patient. In transplant recipients or autoimmune patients, after months to years on the drug, it kills rapidly dividing crypt cells, causing chronic diarrhea, sometimes bloody. Biopsies show crypt apoptosis, crypt distortion and dropout, and mild villous blunting that mimics graft-versus-host disease and rejection. The clue is the timing with the drug. The fix is a lower dose or a switch, to azathioprine, calcineurin inhibitor monotherapy, or another antimetabolite, after excluding graft-versus-host disease, cytomegalovirus, CMV, and rejection.

12:19Two more immunosuppressants complete the drug list. Methotrexate causes dose-related mucositis with crypt apoptosis, villous atrophy, and stomatitis, timed with its doses. Azathioprine rarely causes a sprue-like enteropathy, and its cytopenias are usually the bigger problem.

12:38One drug class injures the bowel through the immune system rather than directly. Immune checkpoint inhibitor enteritis comes from releasing the brakes on T cells with antibodies against cytotoxic T-lymphocyte antigen four, CTLA-4, programmed death one, PD-1, or programmed death-ligand one, PD-L1. The released T cells attack the gut, causing an injury that looks like inflammatory bowel disease. It usually affects the colon more than the small bowel, so it's often called enterocolitis.

13:08Its timing and treatment follow a set sequence. It appears weeks to months into treatment, and the risk is highest with anti-CTLA-4 drugs and combination therapy and lower with PD-1 or PD-L1 blockade alone. Infection, including C. difficile and CMV, is excluded first. The drug is held, steroids are given by severity grade, and infliximab or vedolizumab follows if steroids fail.

13:34The third patient has no drug to blame. A forty-five-year-old woman with Hashimoto thyroiditis and type one diabetes has eight months of high-output watery diarrhea and malabsorption so severe that she needs parenteral nutrition. Her biopsies show villous atrophy with relatively few intraepithelial lymphocytes, prominent deep crypt apoptosis, and almost no goblet or Paneth cells. Celiac serology is negative, the gluten-free diet failed, and she takes no culprit drugs.

14:06That's autoimmune enteropathy, an immune attack against the intestinal lining. The adult form is rare, with high-output secretory diarrhea, severe malabsorption, and weight loss, and in the largest series up to about forty-seven percent needed parenteral nutrition. About ninety percent of adults have antibodies against enterocytes, often also against goblet cells. But the antibodies aren't specific, since olmesartan enteropathy can produce them, and some patients have none.

14:35So the diagnosis rests on a triad. It needs chronic diarrhea with malabsorption, exclusion of celiac disease and other enteropathies including drugs, and the characteristic histology: villous atrophy with loss of goblet and Paneth cells and deep crypt apoptosis. Adults often have other autoimmune diseases, such as thyroiditis, type one diabetes, autoimmune hepatitis, autoimmune gastritis with pernicious anemia, ulcerative colitis, or rheumatoid arthritis. HLA-DQ2 is common here too, so genotype doesn't separate it from celiac disease.

15:14One more test is essential before treating her, because its answer would change the diagnosis. Quantitative immunoglobulins look for common variable immunodeficiency, which also causes chronic diarrhea and villous changes, usually with recurrent sinus and lung infections. Hers are normal.

15:31Her treatment is immunosuppression, because the disease isn't driven by gluten. First-line is budesonide nine milligrams daily, with the capsules opened so the drug is released in the proximal small bowel, where the disease is. About eighty-five percent respond, even some who failed systemic steroids. Second-line options are infliximab, cyclosporine, tacrolimus, mycophenolate, and rituximab, and refractory disease in younger patients can be treated with autologous stem cell transplant. Parenteral nutrition supports her meanwhile.

16:03Her outlook depends on response. Remission is maintained with a thiopurine or low-dose budesonide. In published series, about a third die of refractory malabsorption despite therapy, a third achieve lasting remission, and the rest live with chronic disease.

16:19The childhood form has a single genetic cause. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked, IPEX, syndrome is an X-linked disease of boys from FOXP3 mutations, which regulatory T cells need to develop. It causes severe diarrhea in the first months of life, with type one diabetes, thyroiditis, eczema, and low blood counts, and it's usually fatal without stem cell transplantation.

16:47The fourth patient's clue is his travel history. A thirty-eight-year-old man returned two months ago from six months working in rural India. Shortly before he left, he developed diarrhea that has never stopped, with foul, fatty stools, cramps, bloating, low-grade fevers, and fifteen pounds of weight loss. He has a smooth, sore tongue. His blood count shows a macrocytic anemia, and both folate and B12 are low.

17:11Low folate and low B12 after time in an endemic area is tropical sprue, a post-infectious enteropathy. After an enteric infection, bacteria colonize the upper small bowel and damage the enterocytes. E. coli is the most consistent isolate, and Giardia and other organisms are implicated. The injury slows motility through release of peptide YY from the ileum, which lets the overgrowth persist. The villous atrophy is partial, less severe than in celiac disease but enough to cause malabsorption.

17:46Where and when he got sick both fit. It occurs in people who live in or travel to the Caribbean, including Puerto Rico, Haiti, the Dominican Republic, and Cuba; Venezuela, Colombia, and other parts of Central and South America; the Indian subcontinent and Southeast Asia; tropical Australia; and parts of West Africa and the Middle East. It begins during or shortly after a stay of weeks to months, or within a few months of returning. The onset is often abrupt, so patients can name when it started, unlike the slow course of celiac disease.

18:20His two vitamin deficiencies separate it from celiac disease. Tropical sprue involves the whole small bowel, including the terminal ileum, so both folate and B12 fall, and a macrocytic anemia appears in over half of cases. Celiac disease mainly affects the proximal bowel, causing folate deficiency but usually sparing B12. Iron and fat-soluble vitamin deficiency, low albumin, glossitis, cheilosis, hyperpigmentation, and edema can follow, and lactose intolerance develops early from loss of brush-border enzymes.

18:54His jejunal biopsy shows partial villous atrophy with lymphocytes under the surface, and celiac serology is negative. A D-xylose test would be abnormal, though it's rarely used now. Stool studies are usually unrevealing by this stage. Giardia is excluded with a stool antigen or polymerase chain reaction, PCR, since it causes similar symptoms and is treated with metronidazole or tinidazole. Tropical enteropathy of undernutrition differs by lacking a post-infectious onset.

19:22His treatment is folate plus tetracycline. Folic acid five milligrams twice daily for two weeks, then one milligram three times daily, alone improves over two-thirds of patients, which was known before antibiotics existed. Tetracycline two hundred fifty milligrams four times daily is added, for four to six weeks after returning from an endemic area, and up to six months for someone living there. Ampicillin, five hundred milligrams twice daily for at least four weeks, is the alternative for patients who can't take tetracycline.

19:52His deficiencies are replaced too. B12 is given by injection, one thousand micrograms weekly for four weeks, then monthly for three to six months, with iron, calcium, zinc, and fat-soluble vitamins as needed.

20:05The fifth patient's small bowel disease is an infection that began in his joints. A fifty-six-year-old man works on a dairy farm. For seven years he's had episodes of pain and swelling that move between his knees, ankles, and wrists. He was diagnosed with seronegative arthritis and treated with prednisone, then a tumor necrosis factor, TNF, inhibitor, and his joints improved. But over the past year he's developed diarrhea, twenty-five pounds of weight loss, low-grade fevers, and enlarged lymph nodes. His skin has darkened, and he has ankle swelling with an albumin of two point six.

20:40Years of migratory arthritis, then diarrhea, weight loss, fever, and nodes, worse after immunosuppression, in a farmer, is Whipple disease until proven otherwise. Whipple disease is a systemic infection with Tropheryma whipplei, a gram-positive actinomycete associated with soil and animals, which is why farmers and outdoor workers are classically affected. The typical patient is a middle-aged white man.

21:05The organism's biology explains the disease. It lives inside macrophages. Patients appear to have a subtle defect in macrophage activation, so their macrophages take it up but can't kill it, and it multiplies slowly inside them. The macrophages fill with bacterial debris, and the infection spreads from the small bowel to the joints, lymph nodes, heart, and brain.

21:28That biology also explains why his arthritis was misdiagnosed and why treating it made him worse. Migratory large-joint arthralgias often come first, years and sometimes a decade before gut symptoms, and look like a seronegative spondyloarthropathy without the HLA-B27 association. Then come diarrhea, weight loss, abdominal pain, fever, and lymphadenopathy, and later skin hyperpigmentation, malabsorption, and protein-losing enteropathy, as his darkened skin and swollen ankles show.

22:01Immunosuppression for the presumed arthritis, steroids or a TNF inhibitor, precipitates flares of the intestinal disease, a common pitfall. A middle-aged man with years of migratory arthritis, then diarrhea and weight loss, who worsened after immunosuppression, should prompt consideration of Whipple disease, ideally before the TNF inhibitor.

22:21Two findings, when present, are pathognomonic. The first is oculomasticatory myorhythmia, slow, rhythmic, converging eye movements in time with rhythmic contractions of the chewing muscles. A related form, oculofacial-skeletal myorhythmia, involves the face and limbs. These are the only nervous system findings diagnostic on their own. Cognitive decline, supranuclear ophthalmoplegia, ataxia, myoclonus, seizures, and personality change are less specific. The spinal fluid looks normal but shows periodic acid-Schiff, PAS, positive cells after centrifugation and is positive for T. whipplei by PCR.

23:05The second pathognomonic finding is in the heart. Whipple endocarditis is culture-negative, with indolent valve vegetations and PAS-positive material on the excised valve. Blood-culture-negative endocarditis that's negative for Bartonella, Coxiella, and Brucella should prompt T. whipplei PCR on the valve tissue.

23:24Confirming it takes a small bowel biopsy from the right place. Biopsies come from the distal duodenum and jejunum, because a bulb-only biopsy can miss it. Endoscopy may show yellowish plaques and dilated lymphatics. Under the microscope, the lamina propria is packed with foamy macrophages that stain bright with PAS, displacing the normal glands.

23:47The PAS stain has a dangerous mimic, so one more stain is needed. Mycobacterium avium complex in advanced human immunodeficiency virus, HIV, infection produces the same PAS-positive foamy macrophages, as can Histoplasma. The acid-fast stain separates them, because T. whipplei is acid-fast negative and Mycobacterium avium is acid-fast positive. So a PAS-positive biopsy in a patient who might have HIV isn't Whipple disease until the acid-fast stain is negative. PCR of the biopsy for T. whipplei deoxyribonucleic acid, DNA, confirms the diagnosis and is the preferred confirmatory test. His jejunal biopsies show PAS-positive, acid-fast negative foamy macrophages, and PCR is positive.

24:38Before treatment, every patient needs one more test, even without neurologic symptoms. It's a lumbar puncture, with spinal fluid PCR for T. whipplei and staining of the centrifuged cells. Central nervous system infection can be subclinical, and finding it determines how long induction lasts. His spinal fluid PCR is negative.

24:58Treatment is designed around the brain, because central nervous system relapse is the main late danger, so the antibiotics must cross the blood-brain barrier. Induction is ceftriaxone two grams intravenously daily for two weeks, extended to four weeks for established central nervous system or heart involvement, with meropenem as an alternative. Maintenance is oral trimethoprim-sulfamethoxazole, double strength, twice daily for a year, chosen because it penetrates the brain.

25:26There's an alternative for patients who can't take sulfa. With a sulfa allergy or treatment failure, doxycycline with hydroxychloroquine is used. Hydroxychloroquine raises the pH inside the macrophage compartment where the organism lives, which helps doxycycline work. His TNF inhibitor stops and his steroids are tapered.

25:45Early in treatment, one reaction is expected in patients like him. Immune reconstitution inflammatory syndrome can occur, most likely in a patient previously immunosuppressed for misdiagnosed arthritis. It's managed with corticosteroids, sometimes thalidomide. He gets two weeks of ceftriaxone and starts a year of trimethoprim-sulfamethoxazole. In the second week he has a brief febrile flare, treated with a short steroid course. His diarrhea then resolves, his albumin recovers, and he regains his weight over six months. Relapse, especially in the central nervous system, is the long-term concern, and the reason maintenance lasts a full year.

26:22The last patient's small bowel is crowded with bacteria that belong in the colon. A seventy-one-year-old man had a partial gastrectomy with a Billroth two reconstruction for a bleeding ulcer thirty years ago and has taken omeprazole daily ever since. For a year he's had bloating, a lot of gas, loose fatty stools, and twelve pounds of weight loss. His hemoglobin is ten point one, with a high mean corpuscular volume. His B12 is low, his folate is high, and his vitamin D is low.

26:54A blind loop, decades of acid suppression, bloating, fatty stools, and a low B12 with a high folate point to small intestinal bacterial overgrowth. Bacterial overgrowth is colon-type bacteria multiplying in the small intestine, defined on small bowel aspirate culture as at least one thousand colony-forming units per milliliter. The older cutoff of one hundred thousand is no longer used.

27:20Its causes follow from what normally keeps the small bowel nearly sterile. Three defenses prevent overgrowth. Gastric acid kills swallowed bacteria. Motility, especially the migrating motor complex that sweeps the bowel between meals, clears what survives. Mucosal immunity keeps the rest in check.

27:40Every cause fits one of those failures. Acid fails with long-term proton pump inhibitors, PPIs, the atrophic stomach of autoimmune gastritis, and gastrectomy. Motility fails in scleroderma, with a dilated, weak small bowel; in diabetic autonomic neuropathy; in chronic intestinal pseudo-obstruction; and in gastroparesis. Anatomy causes stasis with small bowel diverticula, strictures, blind loops, a resected ileocecal valve, and the afferent limb after a Billroth two or Roux-en-Y reconstruction.

28:13The remaining causes involve immunity and bile flow. Immune deficiencies such as common variable immunodeficiency, and chronic pancreatitis or cirrhosis, complete the list. He has a Billroth two afferent limb where contents stagnate, a smaller stomach that makes less acid, and decades of acid suppression.

28:34His symptoms follow from what the bacteria do. They ferment carbohydrates, producing gas, bloating, and pain. They deconjugate bile salts, so fat isn't absorbed, causing fatty stools and loss of fat-soluble vitamins, like his low vitamin D. Their enzymes damage brush-border disaccharidases, adding carbohydrate malabsorption and diarrhea. Weight loss follows, and iron deficiency is common too.

29:00His labs show the classic pattern, low B12 with high folate. The bacteria take up B12, and cleave it from intrinsic factor, before the ileum can absorb it, while they make folate, which the bowel absorbs. Tropical sprue, by contrast, lowers both.

29:17Confirming it usually means a breath test, because the reference standard, aspirate culture, is invasive and not widely done. The patient drinks glucose or lactulose, and breath hydrogen is measured over time. A rise of at least twenty parts per million above baseline within ninety minutes indicates overgrowth, because an early rise comes from the small bowel and a late rise is normal colonic fermentation.

29:42Methane is measured too, because it changes the picture. Methane-producing organisms, mainly Methanobrevibacter smithii, cause methane-predominant overgrowth, which goes with constipation rather than diarrhea.

29:55Breath tests mislead in predictable ways. Rapid small bowel transit gives a false positive, because the sugar reaches the colon early and its peak is misread as a small bowel peak. A false negative occurs when the bacteria don't produce hydrogen, or after recent antibiotics. When the test is unavailable or equivocal and suspicion is high, an empiric antibiotic trial is reasonable. His glucose breath test shows a hydrogen rise of thirty-five parts per million at forty-five minutes. With his afferent limb and his low B12 with high folate, that result fits overgrowth.

30:29Treatment has two parts: fix the cause if possible, and treat the bacteria. Scleroderma gets a prokinetic, diabetic neuropathy gets better glucose control, a blind loop gets surgical revision, and unnecessary acid suppression is stopped. He has no ongoing reason for omeprazole thirty years after a healed ulcer, so it stops, but his afferent limb is permanent.

30:54His antibiotic is chosen for tolerability. The first-line antibiotic is rifaximin, five hundred fifty milligrams three times a day for fourteen days, barely absorbed and well tolerated. Alternatives include amoxicillin-clavulanate, ciprofloxacin, doxycycline, and metronidazole. B12, fat-soluble vitamins, and iron are replaced as needed.

31:18Recurrence is the rule when the cause can't be fixed, as with a permanent afferent limb or a motility disorder, because the stagnant bowel is still there. Those patients get cyclic antibiotics, one to two weeks each month, often rotating agents. He takes rifaximin for two weeks, stops omeprazole, and starts B12 injections and vitamin D. His symptoms improve and he regains weight. Four months later his symptoms return, so he moves to cyclic, rotating antibiotics.

31:47Here are the traps the boards set in these patients. A self-diagnosis of gluten sensitivity isn't accepted without excluding celiac disease, and celiac testing isn't done while the patient is gluten-free. A three-month gluten challenge isn't needed when HLA testing can exclude celiac disease. A negative HLA test doesn't exclude gluten sensitivity, and a positive one isn't a diagnosis. Wheat allergy isn't overlooked. And a patient isn't left on blanket FODMAP restriction, or committed to lifelong gluten avoidance when fructans are the trigger.

32:19The villous atrophy traps follow. Seronegative celiac disease isn't diagnosed before the medications are reviewed. Olmesartan isn't restarted to confirm the diagnosis. HLA-DQ2 and anti-enterocyte antibodies don't separate the enteropathies. Quantitative immunoglobulins aren't forgotten, and budesonide capsules are opened for proximal disease. The travel history isn't missed, and tropical sprue isn't treated without B12.

32:48The Whipple traps come next. Migratory arthritis isn't treated with immunosuppression without considering Whipple disease. Biopsies aren't taken only from the duodenal bulb. The acid-fast stain isn't skipped. The lumbar puncture isn't skipped. And maintenance antibiotics have to reach the brain.

33:07The overgrowth traps close the list. Treating only the bacteria misses the cause. The overgrowth vitamin pattern, low B12 with high folate, isn't the tropical sprue pattern. A late colonic peak isn't a positive breath test. Methane goes with constipation. And recurrence is expected when the cause can't be corrected.

33:27So, start to finish. Exclude celiac disease on gluten before any other label, using HLA typing if the patient is already gluten-free. Wheat allergy is rapid and IgE-mediated and needs strict avoidance. Gluten sensitivity is delayed, with normal serology and histology, and isn't excluded by HLA. Fructans, not gluten, explain many self-reported gluten sensitivities, so a dietitian-supervised low-FODMAP diet, eliminate, reintroduce, personalize, is often the better first step.

34:02Villous atrophy with negative serology and no diet response starts with the medication list, and olmesartan sprue resolves when the drug stops. Autoimmune enteropathy loses goblet and Paneth cells and is treated with open-capsule budesonide, after checking immunoglobulins. Tropical sprue lowers both folate and B12 and is treated with tetracycline and folic acid, plus B12.

34:26Whipple disease is T. whipplei persisting in macrophages: years of migratory arthritis, then diarrhea, weight loss, fever, and nodes, often worse after immunosuppression. Oculomasticatory myorhythmia is pathognomonic. Distal duodenal and jejunal biopsies show PAS-positive, acid-fast negative macrophages, confirmed by PCR, and every patient has a lumbar puncture. Treat with ceftriaxone, then a year of trimethoprim-sulfamethoxazole.

34:58Bacterial overgrowth follows failure of acid, motility, or anatomy, with low B12 and high folate. Diagnose with a breath test, treat with rifaximin, fix the cause where possible, and use cyclic antibiotics when it can't be fixed.

35:13The next chapter is chronic diarrhea: how the history, basic labs, and stool studies place a patient into one of four mechanisms, and the second-stage tests for each.

35:23For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of one of chapter eleven, and I'll see you in the next one.